From OHC

November 6, 2024

Non-small cell lung cancer (NSCLC) is a common type of lung cancer that has been challenging to treat, especially in patients with the KRAS G12C mutation. For nearly 40 years, targeting this mutation has been elusive. However, sotorasib, a newer medication, has shown promise in effectively targeting KRAS G12C.

Sotorasib was originally evaluated from June 2020 to the spring of 2021 to determine its efficacy on treating NSCLC.  OHC proudly participated in this initial clinical trial and OHC medical oncologist and hematologist David M. Waterhouse, MD, MPH, was an original author of the report of the CodeBreak 200 trial, which evaluated sotorasib vs the standard of care medication, docetaxel.  Patient-reported outcomes (PROs) were key to the Food and Drug Administration’s (FDA) approval of sotorasib for the treatment of NSCLC.  Dr. Waterhouse recently published a follow-up article, explaining the importance of PROs in this trial and how they contribute to the assessment of new therapies.

The CodeBreak 200 trial was a randomized, phase III study involving 345 patients with advanced NSCLC who had the KRAS G12C mutation. Participants were divided into two groups: one received sotorasib (960 mg orally daily), and the other received docetaxel (75 mg/m² intravenously every three weeks). The study aimed to evaluate not only the efficacy of these treatments but also the quality of life and side effects as reported by the patients themselves.

The key findings included the following:

Efficacy and Safety

  • Sotorasib significantly improved progression-free survival (PFS) compared to docetaxel (5.6 months vs. 4.5 months).
  • The objective response rate (ORR) was higher for sotorasib (28.1%) compared to docetaxel (13.2%).
  • Sotorasib showed a lower incidence of severe treatment-related adverse events (33% vs. 40%).

Patient-Reported Outcomes

  • Patients on sotorasib reported fewer and less severe side effects.
  • Symptoms such as pain, aching muscles, aching joints, and mouth or throat sores were less bothersome for those taking sotorasib.
  • Quality of life remained stable for patients on sotorasib but worsened for those on docetaxel.

According to Dr. Waterhouse, “Historically we have looked at toxicity through the lens of the provider.  Our interpretation of the significance of the toxicity can often differ from that of the patients’.  Looking at toxicity through the lens of the patient allows us to understand how they are experiencing the toxicity and the impact that the toxicity has on their quality of life.”

By focusing on PROs, the study highlighted that patients on sotorasib experienced:

  • Less interference from symptoms in daily activities.
  • Better overall health and quality of life compared to those on docetaxel.
  • Significant improvements in mobility, self-care, and usual activities.

“Sotorasib was the first agent to successfully target KRAS. This target has been very difficult to address despite the fact that we have known about it for nearly 40 years.  The approval was based on the improved progression-free survival and patient-reported outcomes,” adds Dr. Waterhouse.

Clinical trials like CodeBreak 200 are pivotal in advancing oncology care. They provide critical data that informs treatment guidelines and offers new hope to patients facing difficult-to-treat cancers. The success of sotorasib in this study highlights the importance of continued investment in innovative research and the development of targeted therapies.

OHC’s involvement in such trials reflects our commitment to being at the forefront of cancer research. Through collaboration with leading researchers and participation in groundbreaking studies, we strive to bring the latest and most effective treatments to our patients each and every day.

To learn more about OHC’s cancer research and clinical trials program, SCRI at OHC, please visit ohcare.com/ohc-clinical-trials-program/.